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Abstract Generative adversarial networks (GAN) in medicine are valuable techniques for augmenting unbalanced rare data, anomaly detection, and avoiding patient privacy issues. However, there were limits to generating high-quality endoscopic images with various characteristics, such as peristalsis, viewpoints, light sources, and mucous patterns. This study used the progressive growing of GAN (PGGAN) within the normal distribution dataset to confirm the ability to generate high-quality gastrointestinal images and investigated what barriers PGGAN has to generate endoscopic images. We trained the PGGAN with 107,060 gastroscopy images from 4165 normal patients to generate highly realistic 5122 pixel-sized images. For the evaluation, visual Turing tests were conducted on 100 real and 100 synthetic images to distinguish the authenticity of images by 19 endoscopists. The endoscopists were divided into three groups based on their years of clinical experience for subgroup analysis. The overall accuracy, sensitivity, and specificity of the 19 endoscopist groups were 61.3%, 70.3%, and 52.4%, respectively. The mean accuracy of the three endoscopist groups was 62.4 [Group I], 59.8 [Group II], and 59.1% [Group III], which was not considered a significant difference. There were no statistically significant differences in the location of the stomach. However, the real images with the anatomical landmark pylorus had higher detection sensitivity. The images generated by PGGAN showed highly realistic depictions that were difficult to distinguish, regardless of their expertise as endoscopists. However, it was necessary to establish GANs that could better represent the rugal folds and mucous membrane texture.

As industrial safety increases, various industrial accident prevention technologies using smart factory technology are being studied. However, small and medium enterprises (SMEs), which account for the majority of industrial accidents, are having difficulties in preventing industrial accidents by applying these smart factory technologies due to practical problems. In this study, customized monitoring and warning systems for each type of industrial accident were developed and applied to the actual field. Through this, we demonstrated industrial accident prevention technology through appropriate smart factory technology used by SMEs. A customized monitoring system using vision, current, temperature, and gas sensors was established for the four major disaster types: worker body access, short circuit and overcurrent, fire and burns due to high temperature, and emission of hazardous gas. In addition, a notification method suitable for each work environment was applied so that the monitored risk factors could be recognized quickly, and real-time data transmission and display enabled workers and managers to understand the disaster risk effectively. Through the application and demonstration of these appropriate smart factory technologies, the spread of these industrial safety technologies is to be discussed.

본 연구에서는 리그닌 기반 다공성 탄소(lignin-based porous carbon; LBPC)를 수산화칼륨(KOH)으로 활성화할 때 온도가 비표면적과 전기화학적 특성에 미치는 영향을 알아보았다. 리그닌과 acrylonitrile을 그라프트 중합으로 합성한 리그닌-polyacrylonitrile (PAN) 공중합체를 전구체로 하여 LBPC를 제조한 후 LBPC를 KOH로 600, 700, 800, 900℃에서 활성화하여 활성화 처리한 LBPC (KA-LBPC-6, 7, 8, 9)를 제조하였다. KA-LBPC의 표면 특성을 알아보기 위해 주사전자현미경으로 관찰하였으며, 비표면적 분석을 통해 기공 특성을 파악하였다. 전기화학적 특성은 3전극 시스템으로 분석하였다. 실험 결과 SEM 사진상에서 활성화 처리에 의한 미세기공 형성을 관찰하였다. KA-LBPC-7의 비표면적은 2480.1 ㎡/g, 미세기공 부피는 0.64 ㎤/g, 중기공 부피는 0.76 ㎤/g으로 KA-LBPC 중에서 가장 좋은 기공 특성을 보였다. 전기화학적 특성 역시 2 mV/s의 주사속도에서 비정전용량이 151.3 F/g이었던 KA-LBPC-7이 가장 좋은 것으로 나타났다.

Fenbendazole (FZ) is a benzimidazole carbamate drug with broad-spectrum antiparasitic activity in humans and animals. The mechanism of action of FZ is associated with microtubular polymerization inhibition and glucose uptake blockade resulting in reduced glycogen stores and decreased ATP formation in the adult stages of susceptible parasites. A completely cured case of lung cancer became known globally and greatly influenced the cancer community in South Korea. Desperate Korean patients with cancer began self-administering FZ without their physician’s knowledge, which interfered with the outcome of the cancer treatment planned by their oncologists. On the basis of presented evidence, this review provides valuable information from PubMed, Naver, Google Scholar, and Social Network Services (SNS) on the effects of FZ in a broad range of preclinical studies on cancer. In addition, we suggest investigating the self-administration of products, including supplements, herbs, or bioactive compounds, by patients to circumvent waiting for long and costly FZ clinical trials.

Characteristics of a discharged liquid jet in near-nozzle are determined by the in-flow turbulences generated by the evolution of inflow vortices and cavitation. High-fidelity simulations have indicated that such physical processes can generate ultrafast turbulent fluctuations (in the range of MHz) originating from the nature of turbulence by the interaction between the large and small-scale turbulence in the flow. Detecting ultrafast turbulent oscillations while resolving small-scale turbulences in the optically dense near-nozzle liquid jet has not been observed through experimental methods so far. In this study, therefore, ultrafast x-ray phase-contrast imaging, which can provide a clear image in the near-field using a high-energy x-ray source, was applied to observe the fluctuation of flow velocity in the near-field to obtain the ultrafast turbulent oscillations at the discharged jet. To capture the ultrafast variance of flow velocity originating from the nature of turbulence, the high imaging frequency was applied up to 1.2 MHz. With the implemented methodology, turbulence intensity distributions of discharged liquid jets were measured for various injection pressures and nozzle geometries. Such turbulence intensity results were also correlated with the initial dispersion angle of the spray. In addition, the turbulence length scales, which can be detected through the current methodology, were estimated and discussed considering standard-length scales. The results showed that the current experimental method introduced in this study can provide important insights into the turbulence characteristics of spray by resolving Taylor scale turbulences and can provide valuable validation data and boundary conditions for reliable spray simulations.

Background and purpose Kaempferol is a natural flavonoid widely investigated in various fields due to its antioxidant, anti-cancer, and anti-inflammatory activities, but few studies have shown its inhibitory effect on T cell activation. This study examined the therapeutic potential of kaempferol in atopic dermatitis by modulating T cell activation. Experimental approach Effects of kaempferol on T cell activation and the underlying mechanisms were investigated in Jurkat cells and mouse CD4+ T cells. A model of atopic dermatitis in mice was used to determine its therapeutic potential on T cell-mediated conditions in vivo. Western blots, RT-PCR, pulldown assays and ELISA were used, along with histological analysis of skin. Key results Pretreatment with kaempferol reduced CD69 expression and production of inflammatory cytokines including IL-2 from activated Jurkat cells and murine CD4+ T cells without cytotoxicity. Pulldown assays revealed that kaempferol physically binds to MRP-1 in T cells, inhibiting the action of MRP-1. In activated T cells, kaempferol suppressed JNK phosphorylation and the TAK1-IKKα mediated NF-κB pathway. Oral administration of kaempferol to mice showed improved manifestation of atopic dermatitis, a T cell-mediated condition. Western blot results showed that, as in the in vitro studies, decreased phosphorylation of JNK was associated with down-regulated MRP-1 activity in vivo, in the kaempferol-treated mice in the atopic dermatitis model. Conclusion and implications Kaempferol regulates T cell activation by inhibiting MRP-1 activity in activated T cells, thus showing protective effects against T cell mediated disease in vivo.

Persimmon leaf extracts (PLE) have been widely used as a traditional medicine in East Asian countries. The effects of persimmon leaves, including antioxidant, antiinflammatory, hypotensive, and anti-allergy effects, have been investigated; however, there is little evidence on the inhibition of T cell activation in vitro and effects on T cell-related diseases, such as atopic dermatitis (AD), in vivo by persimmon leaves. PLE (50 μg/mL) effectively attenuated the mRNA levels of IL-2 in Jurkat T cells stimulated with PMA/A23187 and Staphylococcus enterotoxin E-loaded Raji B cells without causing cytotoxicity. In Jurkat T cells stimulated with PMA/A23187, treatment with 50 μg/mL PLE blocked the translocation of p65 and IκBα degradation. Moreover, the JNK signaling pathway in Jurkat T cells stimulated with PMA/A23187 was affected by treatment with PLE. The oral administration of PLE markedly attenuated AD manifestations in mice, including ear thickness, IgE levels, and lymph node sizes. These results indicate PLE significantly blocked T cell activation via NF-κB signaling and the JNK pathway. This suggests underlying mechanisms of PLE involving the control of effector cytokines produced by activated T cells in ear tissue and lymph nodes, as well as the infiltration of mast cells and the therapeutic potential of AD.

Smart factory is the main keyword in the field of manufacturing processes about the fourth industrial revolution. To realize the smart factory, making all pieces of device into smart devices that are connected to the centralized system to enable a real-time exchange of information is essential. Sound can be efficient means to make devices as smart devices because sound can contain the status information of various devices simultaneously, and it can be recorded easily outside of a device using only a microphone. In this study, multi-device operation monitoring system by analyzing sound is developed. Mic arrays for acquiring the sound were installed at the outside the devices and recorded the sounds from several devices simultaneously. By analyzing the recorded sound with log-mel spectrogram and Convolutional Neuron Network (CNN), the system could detect the operational status of three devices with an accuracy of 71–92 %. To improve the performance, virtual data set was created by composition of individual device operating sounds of different intensities. With this virtual data set, accuracy can be enhanced to 87 % ∼ 99 % accuracy and, required sound data amount could be reduced. Developed system was applied successfully in monitoring experiments in two different environments: a workshop in which hand-operated device was used and a factory with a computer numerical control machine and verifying the performance.

Methamphetamine (METH) is an extremely addictive drug that has raised serious public health concerns recently. METH addiction not only results in neuronal cytotoxicity, but it also affects immune cell activity, including T lymphocytes. 6,4,7[Formula: see text]-trihydroxyflavanone (THF), isolated from Dalbergia odorifera, has been studied for its antibacterial activity, but evidence for whether THF has an anti-cytotoxic and protective effect on T cell activation exposed to METH is lacking. In this study, results showed that treatment with THF was not cytotoxic to Jurkat T cells but dose-dependently mitigated the cytotoxicity induced by exposure to METH. The Western blot results demonstrating pre-treatment with THF maintained the expression of anti-apoptotic proteins and phosphorylation of PI3K/Akt/mTOR downregulated by treatment with METH. Furthermore, we found that decreased expression of IL-2 and CD69 by METH exposure was partially restored, and viability was significantly prevented by pre-treatment with THF in activated T cells. These findings were involved in re-elevated expression of anti-apoptotic proteins as well as recovered pathways including MAPK/PI3K/Akt/mTOR in activated T cells pre-exposed to METH. Our results suggest beneficial effects of THF against the cytotoxic and immune-modulating effect of METH on T cells and therapeutic potential of THF for patients with immunodeficiency caused by METH addiction.

The material extrusion (ME) process is one of the most widely used 3D printing processes, especially considering its use of inexpensive materials. However, the error known as the “spaghetti-shape error,” related to filament tangling, is a common problem associated with the ME process. Once occurring, this issue, which consumes both time and materials, requires a restart of the entire process. In order to prevent this, the user must constantly monitor the process. In this research, a failure detection method which uses a webcam and deep learning is developed for the ME process. The webcam captures images and then analyzes them by machine learning based on a convolutional neural network (CNN), showing outstanding performance in both image classification and the recognition of objects. Sample images were trained based on a modified Visual Geometry Group Network (VGGNet) model and the trained model was evaluated, resulting in 97% accuracy. The pre-trained model was tested on a 3D printer monitoring system for its ability to recognize the “spaghetti-shape-error” and was able to detect 96% of abnormal deposition processes. The proposed method can analyze the ME process in real time and informs the user or halts the process when abnormal printing is detected.

The precise location of the Master Knot of Henry (MKH) has important clinical significance, but its anatomical definition has not been agreed upon. The purpose of this study is to present a linear regression equation for predicting length variables based on foot length, by evaluating the correlation of length variables related to flexor hallucis longus (FHL) and flexor digitorum longus (FDL), with respect to the location of the MKH. A total of 95 limbs were dissected from 48 adult cadavers, and were fixed in formalin. Measurements were made for the length parameter, with reference to the landmark. The relevance between length variables was analyzed through simple correlation analysis and linear regression analysis. The foot length was 213.69 ± 17.53 mm, MKH-great toe distal phalanx was 140.16 ± 14.69 mm, MKH-FHL insertion was 124.55 ± 13.46 mm, MKH-little toe distal phalanx was 121.79 ± 13.41 mm, MKH-FDL little toe insertion was 109.07 ± 14.16 mm, and the FHL-FDL angle was 33.15 ± 5.39. The correlation coefficient between all the length variables for foot length showed a high positive correlation. We derived a regression equation that can predict the length of each variable. This regression formula is considered to be highly useful because it can estimate the positional relationship of the MKH relatively simply.

Background and objectives: EZH2 is overexpressed in hepatocellular carcinoma (HCC) and is correlated with poor prognosis. However, its clinical significance and molecular mechanism have not been studied in HCC. In this study, clinical and prognostic values of EZH2 was studied using Total Cancer Genome Atlas (TCGA) data and then, these data were confirmed in Huh1 and HepG2 cell lines. Materials and Methods: We used the TCGA database from cBioPortal. In addition, we analyzed EZH2 mRNA levels in HCC cell lines and its correlation with STAT3 and EZH2. Results: According to TCGA, EZH2 had a prognostic value in various cancers, especially in HCC. Furthermore, EZH2 in HCC was correlated with N stage (p = 0.045) and alpha-fetoprotein (AFP) > 20 ng/mL (p < 0.01). However, a negative association between EZH2 and age (p = 0.027) was found. The overall survival result of HCC was significantly poorer in patients with high EZH2 expression. In addition, the recurrence rate was also significantly higher in patients with high expression of EZH2 than those with low expression (χ2 = 16.10, p < 0.001). EZH2 expression was negatively correlated with STAT3 expression among EZH2-associated genes (R = −0.163, p = 0.002). EZH2 expression level was down-regulated to 50% or less compared to the control group treated negative siRNA. MTT assays showed that EZH2-siRNA affected on the viability of HCC cell line significantly. Conclusions: In conclusion, the overexpression of EZH2 was an independent biomarker for poor outcomes of HCC. However, more in vivo studies are required to identify the downstream target genes in HCC to improve our understanding of the biological role of EZH2 in HCC.

Triacsins are a family of natural products containing an N-hydroxytriazene moiety not found in any other known secondary metabolites. Though many studies have examined the biological activity of triacsins in lipid metabolism, the biosynthesis of triacsins has remained unknown. Here, we report the identification of the triacsin biosynthetic gene cluster in Streptomyces aureofaciens ATCC 31442. Bioinformatic analysis of the gene cluster led to the discovery of the tacrolimus producer Streptomyces tsukubaensis NRRL 18488 as a new triacsin producer. In addition to targeted gene disruption to identify necessary genes for triacsin production, stable isotope feeding was performed in vivo to advance the understanding of N-hydroxytriazene biosynthesis.

The endoscopic features between herpes simplex virus (HSV) and cytomegalovirus (CMV) esophagitis overlap significantly, and hence the differential diagnosis between HSV and CMV esophagitis is sometimes difficult. Therefore, we developed a machine-learning-based classifier to discriminate between CMV and HSV esophagitis. We analyzed 87 patients with HSV esophagitis and 63 patients with CMV esophagitis and developed a machine-learning-based artificial intelligence (AI) system using a total of 666 endoscopic images with HSV esophagitis and 416 endoscopic images with CMV esophagitis. In the five repeated five-fold cross-validations based on the hue–saturation–brightness color model, logistic regression with a least absolute shrinkage and selection operation showed the best performance (sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under the receiver operating characteristic curve: 100%, 100%, 100%, 100%, 100%, and 1.0, respectively). Previous history of transplantation was included in classifiers as a clinical factor; the lower the performance of these classifiers, the greater the effect of including this clinical factor. Our machine-learning-based AI system for differential diagnosis between HSV and CMV esophagitis showed high accuracy, which could help clinicians with diagnoses.

Immune checkpoint blockade therapy has provided clinical benefit to some patients with advanced cancer including melanoma and non-small cell lung cancer. However, many patients still fail to respond to single immune checkpoint blockade therapy. The need for combination therapies to increase anti-tumor responses is becoming important. Interleukin-4 receptor (IL4R) is frequently overexpressed in various cancer types and promotes tumor cell survival. PD-L1, a well-known immune checkpoint, is up-regulated in malignant tumors and inhibits T-cell activity. In this study, we aimed at a combination therapy using an IL4R-targeted cytotoxic peptide and PD-L1-blocking peptide. To target IL4R-high tumor cells, we exploited IL4RPep-1-KLA composed of IL4RPep-1, an IL4R-binding peptide, and (KLAKLAK)2, a cytotoxic peptide. IL4RPep-1-KLA induced necrosis as well as apoptosis of IL4R-expressing tumor cells and increased the secretion of CRT, HMGB1, and ATP, well-known markers of immunogenic cell death (ICD). Flow cytometry analysis showed that the conditioned medium of tumor cells treated with IL4RPep-1-KLA enhanced the expression of CD86 and CD80 on dendritic cells, suggesting the activation and maturation of dendritic cells through ICD. Sequential treatment with IL4RPep-1-KLA followed by PD-L1Pep-2, a PD-L1-blocking peptide, during the co-culture of tumor cells and CD8+ T-cells activated T-cell activity including T-cell proliferation and cytokine secretion more efficiently than single treatment with IL4RPep-1-KLA or PD-L1Pep-2, or simultaneous treatment. These results suggest that sequential, combined treatment with the IL4R-targeted cytotoxic peptide and PD-L1-blocking peptide can induce ICD of tumor cells and maturation of dendritic cells and subsequently activate T-cells. This treatment is a promising strategy for cancer immunotherapy. Citation Format: Nawon Park, Byungheon Lee, Hyunsu Lee. Combined treatment with interleukin-4 receptor-targeted cytotoxic peptide and PD-L1-blocking peptide efficiently induces immunogenic cell death of tumor cells and activates T-cell activity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3422.

BACKGROUND Generative adversarial networks(GAN) in medicine is a valuable technique for augmenting unbalanced data, anomaly detection, learning representation, and avoiding patient privacy issues. However, there were limitations in generating highly realistic endoscopic images with various characteristics, such as peristalsis, viewpoints, light sources, artifacts, and mucous patterns. OBJECTIVE The purpose of this study is to evaluate the ability to generate gastrointestinal images using a progressive growing GAN(PGGAN) within the distribution of a normal dataset and to investigate obstacles of PGGAN in compositing high-quality endoscopic images. METHODS We trained the PGGAN with 107,060 normal gastroscopy images obtained from 4,165 normal patients 5122 pixels images. For the evaluation, visual Turing tests were conducted by endoscopists on 200 images(randomly selected 100 real and 100 synthetics) to distinguish the authenticity of the images. Nineteen endoscopists were divided into three groups to determine differences in discernment based on clinical experience.(Twelve endoscopists with 0-5 yrs experience[Group I], three endoscopists with 5-10 yrs experience[Group II], four endoscopists more than 10 yrs experience[Group III]). In addition, subgroup analysis by anatomical structures was performed to analyze 100 generated images. RESULTS The overall accuracy, sensitivity, and specificity of the nineteen endoscopists were 61.3, 70.3, and 52.4%, respectively. The mean accuracy of the three endoscopist groups was 62.4[Group I], 59.8[Group II], and 59.1 %[Group III], which was not shown a meaningful difference(P=.73). There were no statistical differences in the locations and forward/retroflexion view of the stomach. However, in sensitivity to anatomical landmarks, the sensitivity to the pylorus was higher than in other locations(P=.002). The discontinuous gastric folds in the stomach were the main reason for endoscopists to detect the generated image as a fake image. CONCLUSIONS The images generated by PGGAN showed highly realistic depictions that were difficult to distinguish for 5122 pixels images. However, it has limitations in generating gastric folds in high-resolution images. CLINICALTRIAL

Peripheral nerve injury results in significant sensory and motor functional deficits. Although direct neurorrhaphy in the early phase may reduce its devastating effects, direct end-to-end neurorrhaphy is sometimes impossible owing to a defect at the injured site of the nerve. Autogenous nerve graft is a primary consideration for peripheral nerve defects; however, significant morbidity of the donor site is inevitable. Recently, the treatment using engineered synthetic nerve conduits has been regarded as a promising strategy to promote the regeneration of peripheral nerve defects. In this study, we developed longitudinally oriented collagen hydrogel-grafted elastic nerve guidance conduits (NGC) to reconstruct sciatic nerve defects. An elastic NGC was prepared by using poly(lactide-co-caprolactone) (PLCL), and electrospun PLCL was adopted to fabricate nanoporous structures with appropriate permeability for nerve regeneration. Oriented collagen hydrogels were prepared by the 3D printing method to achieve a microscale hydrogel pattern. Based on sciatic nerve injury models in rats, we confirmed the beneficial effects of the NGC with 3D printed collagen hydrogel on axonal regeneration and remyelination along with superior functional recovery in comparison with the NGC filled with the bulk collagen hydrogel. It is believed that the aligned collagen hydrogels provide a preferable environment for nerve regeneration, functioning as an oriented guidance path. In conclusion, the PLCL nerve guide conduit containing a 3D printed aligned collagen hydrogel can be useful for peripheral nerve regeneration.

The epithelium forms a protective barrier against external biological, chemical and physical insults. So far, AFM-based, micro-mechanical measurements have only been performed on single cells and confluent cells, but not yet on cells in the physiologically relevant, mature epithelial layer.Using a combination of atomic force, fluorescence and confocal microscopy, we determined the changes in stiffness, morphology and actin distribution of human mammary epithelial cells (HMECs) as they transition from single cells to confluency to a mature epithelial layer.Single cells have a tall, round (planoconvex) morphology, have actin stress fibers at the base, have diffuse cortical actin, and have a stiffness of 1 kPa. Confluent cells become flatter, basal actin stress fibers start to disappear, and actin accumulates laterally where cells abut. Overall stiffness is still 1 kPa with two-fold higher stiffness in the abutting regions. Cells in an epithelial layer are flat on top and seven times stiffer (average, 7 kPa) than single and confluent cells. Epithelial layer cells show strong actin accumulation in the regions where cells adjoin and in the apical regions. Stiffness is significantly enhanced in the regions of adjoining cells, compared to the central regions of cells.Physiologically, this previously unrecognized, drastic stiffness increase may be important to the protective function of the epithelium.

The hippocampus is an essential brain region for spatial memory and learning. Recently, a theoretical model of the hippocampus based on temporal difference (TD) learning has been published. Inspired by the successor representation (SR) learning algorithms, which decompose value function of TD learning into reward and state transition, they argued that the rate of firing of CA1 place cells in the hippocampus represents the probability of state transition. This theory, called predictive map theory, claims that the hippocampus representing space learns the probability of transition from the current state to the future state. The neural correlates of expecting the future state are the firing rates of the CA1 place cells. This explanation is plausible for the results recorded in behavioral experiments, but it is lacking the neurobiological implications. Modifying the SR learning algorithm added biological implications to the predictive map theory. Similar with the simultaneous needs of information of the current and future state in the SR learning algorithm, the CA1 place cells receive two inputs from CA3 and entorhinal cortex. Mathematical transformation showed that the SR learning algorithm is equivalent to the heterosynaptic plasticity rule. The heterosynaptic plasticity phenomena in CA1 were discussed and compared with the modified SR update rule. This study attempted to interpret the TD algorithm as the neurobiological mechanism occurring in place learning, and to integrate the neuroscience and artificial intelligence approaches in the field., 9 pages, 1 figure

The cleaning efficiency of salt cleaning and osmotic backwash in a nanofiltration (NF) process is evaluated using model organic foulants in the presence of calcium ions (Ca2+). In particular, the organic fouling behavior—which depends on Ca2+ concentration—and cleaning mechanism in both salt cleaning and osmotic backwash are studied. The results show that Ca2+ aggravates organic fouling, and the fouling formation rate is affected by the Ca2+/foulant ratio. Salt cleaning and osmotic backwash effectively clean Ca2+-bridging fouling, and the important cleaning mechanism in both methods is ion-exchange between the monovalent and divalent cations, resulting in the breakup of Ca2+–foulant binding and Ca2+-induced intermolecular bridging. The cleaning efficiency of osmotic backwash is 26% higher than that of salt cleaning, primarily owing to that the backwash flux creates synergy effect with ion-exchange to removes the weakened fouling structure on the membrane surface. In addition, the cleaning efficiency for irreversible fouling is of the order of osmotic backwash > chemical cleaning > salt cleaning, and osmotic backwash exhibited a 7.3% and 20.8% higher cleaning efficiency than chemical cleaning and salt cleaning, respectively. Therefore, osmotic backwash can stably maintain NF membrane performance for organic fouling and potentially replace the traditional chemical cleaning.

Mutations in the promoter region of telomerase reverse transcriptase (TERT) and alterations in telomere length (TL) have been the focus of research in various types of cancer. In the present study, the frequency and clinical characteristics of TERT promoter mutations and TL were studied in non-small cell lung cancers (NSCLC). TERT promoter mutations and TL were analyzed in 188 patients using DNA sequencing and the reverse transcription-quantitative polymerase chain reaction, respectively. The TERT promoter mutation rate was observed to be 2.2% (4/188 NSCLC cases), and it was significantly associated with regional lymph node invasion (P

Triacsins are a family of natural products containing an N-hydroxytriazene moiety not found in any other known secondary metabolites. Though many studies have examined the biological activity of triacsins in lipid metabolism, the biosynthesis of triacsins has remained unknown. Here, we report the identification of the triacsin biosynthetic gene cluster inStreptomyces aureofaciensATCC 31442. Bioinformatic analysis of the gene cluster led to the discovery of the tacrolimus producerStreptomyces tsukubaensisNRRL 18488 as a new triacsin producer. In addition to targeted gene disruption to identify necessary genes for triacsin production, stable isotope feeding was performedin vivoto advance the understanding of N-hydroxytriazene biosynthesis.

Cannabis sativa L. has been cultivated and used around the globe for its medicinal properties for millennia 1 . Some cannabinoids, the hallmark constituents of Cannabis, and their analogues have been investigated extensively for their potential medical applications 2 . Certain cannabinoid formulations have been approved as prescription drugs in several countries for the treatment of a range of human ailments 3 . However, the study and medicinal use of cannabinoids has been hampered by the legal scheduling of Cannabis, the low in planta abundances of nearly all of the dozens of known cannabinoids 4 , and their structural complexity, which limits bulk chemical synthesis. Here we report the complete biosynthesis of the major cannabinoids cannabigerolic acid, Δ 9 -tetrahydrocannabinolic acid, cannabidiolic acid, Δ 9 -tetrahydrocannabivarinic acid and cannabidivarinic acid in Saccharomyces cerevisiae, from the simple sugar galactose. To accomplish this, we engineered the native mevalonate pathway to provide a high flux of geranyl pyrophosphate and introduced a heterologous, multi-organism-derived hexanoyl-CoA biosynthetic pathway 5 . We also introduced the Cannabis genes that encode the enzymes involved in the biosynthesis of olivetolic acid 6 , as well as the gene for a previously undiscovered enzyme with geranylpyrophosphate:olivetolate geranyltransferase activity and the genes for corresponding cannabinoid synthases 7,8 . Furthermore, we established a biosynthetic approach that harnessed the promiscuity of several pathway genes to produce cannabinoid analogues. Feeding different fatty acids to our engineered strains yielded cannabinoid analogues with modifications in the part of the molecule that is known to alter receptor binding affinity and potency 9 . We also demonstrated that our biological system could be complemented by simple synthetic chemistry to further expand the accessible chemical space. Our work presents a platform for the production of natural and unnatural cannabinoids that will allow for more rigorous study of these compounds and could be used in the development of treatments for a variety of human health problems.

This study aimed to evaluate the effects of cinnamamides on atopic dermatitis (AD) and the mechanisms underlying these effects. To this end, the actions of two cinnamamides, (E)-3-(4-hydroxyphenyl)-N-phenylethyl acrylamide (NCT) and N-trans-coumaroyltyramine (NCPA), were determined on AD by orally administering them to mice. Oral administration of the cinnamamides ameliorated the increase in epidermal and dermal thickness as well as mast cell infiltration. Cinnamamides suppressed serum immunoglobulin (Ig) levels and expression of T-helper (Th)1/Th2 cytokines. Moreover, cinnamamides suppressed interleukin (IL)-4, which plays a crucial role in preparing naïve clusters of differentiation (CD)4+ T cells, and decreased the cervical lymph node size and weight. Interestingly, in almost all cases, NCPA exhibited higher anti-AD activity compared to NCT. These results strongly indicate that NCPA may have potential as an anti-AD agent, and further mechanistic comparative studies of NCT and NCPA are required to determine the cause of differences in biological activity.

Osteoarthritis (OA) is a common joint degenerative disease induced by oxidative stress in chondrocytes. Although induced-heme oxygenase-1 (HO-1) has been found to protect cells against oxygen radical damage, little information is available regarding the use of bioactive compounds from natural sources for regulating the HO-1 pathway to treat OA. In this study, we explored the inhibitory effects of cudratricusxanthone O (CTO) isolated from the Maclura tricuspidata Bureau (Moraceae) on H2O2-induced damage of SW1353 chondrocytes via regulation of the HO-1 pathway. CTO promoted HO-1 expression by enhancing the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) into the nucleus without inducing toxicity. Pretreatment with CTO-regulated reactive oxygen species (ROS) production by inducing expression of antioxidant enzymes in H2O2-treated cells and maintained the functions of H2O2-damaged chondrocytes. Furthermore, CTO prevented H2O2-induced apoptosis by regulating the expression of anti-apoptotic proteins. Treatment with the HO-1 inhibitor tin-protoporphyrin IX revealed that these protective effects were exerted due to an increase in HO-1 expression induced by CTO. In conclusion, CTO protects chondrocytes from H2O2-induced damages&mdash, including ROS accumulation, dysfunction, and apoptosis through activation of the Nrf2/HO-1 signaling pathway in chondrocytes and, therefore, is a potential therapeutic agent for OA treatment.

Author(s): Luo, Xiaozhou; Reiter, Michael A; d'Espaux, Leo; Wong, Jeff; Denby, Charles M; Lechner, Anna; Zhang, Yunfeng; Grzybowski, Adrian T; Harth, Simon; Lin, Weiyin; Lee, Hyunsu; Yu, Changhua; Shin, John; Deng, Kai; Benites, Veronica T; Wang, George; Baidoo, Edward EK; Chen, Yan; Dev, Ishaan; Petzold, Christopher J; Keasling, Jay D | Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Methamphetamine (METH) is an addictive psychostimulant showing neurotoxicity through neuronal apoptosis and the neuro-inflammatory pathway. Lupenone, a lupane triterpenoid, is an isolated compound exhibiting anti-oxidative, anti-inflammation, and anti-diabetic activities. However, whether lupenone plays a protective role against apoptosis induced by METH in SH-SY5y neuroblastoma cells remains unknown. In the present study, we elucidated that lupenone had no toxicity to SH-SY5y cells at different concentrations. On the other hand, we found that the treatment of SH-SY5y cells with an optimal concentration of lupenone could lead to protection against cell death induced by METH. AnnexinV/PI apoptosis analysis revealed a dramatically reduced level of the apoptotic cell population in lupenon and METH treated SH-SY5y cells. Moreover, diminished expression of anti-apoptotic proteins, including Bcl-2, Caspase3, Caspase7, and Caspase8 in METH-exposed SH-SY5y cells, was significantly recovered by treatment with lupenone. This protection in the expression of anti-apoptotic proteins was due to an increased phosphorylation level of PI3K/Akt in METH-treated SH-SY5y cells pre-incubated with lupenone. These findings suggest that lupenone can protect SH-SY5y cells against METH-induced neuronal apoptosis through the PI3K/Akt pathway.

The task of classifying and identifying neurons, the essential components of the nervous system, has been undertaken in a variety of ways. The transcriptomic approach has become more accessible with the development of genetic engineering techniques. Considering the information processing function of the brain, however, it is necessary to consider the physiological characteristics of neurons. Recently, the Allen Institute for Brain Science has published the electrophysiological characteristics of neurons which were tagged with a transgenic reporter. We used these electrophysiological features to predict the transgenic markers of neurons. Using linear regression, random forest, and an artificial neural network, we assessed the performance of supervised machine learning models by comparing the prediction accuracy or the confusion matrix. As a result, in the binary classification problem of classifying excitatory and inhibitory neurons, the accuracy was 90% or more regardless of the model. The models showed better performance than merely distinguishing neurons by suprathreshold features such as the ratio of upstrokes and downstrokes of a single spike (ρ). However, when excitatory neurons were classified, the accuracy was 28˜47%, and the accuracy of classifying inhibitory neurons was 59˜73%. The present study was based on the results of electrophysiological experiments to determine whether transgenic markers of neurons could be predicted. Future research is needed to acquire electrophysiological data and transcriptomic data simultaneously on the single cell level to reveal the correlation between the gene expression and the physiological function of a neuron in building the neural network.

Efficient injection of charge carriers from the contacts into the semiconductor layer is crucial for achieving high-performance organic devices. The potential drop necessary to accomplish this process yields a resistance associated with the contacts, namely the contact resistance. A large contact resistance can limit the operation of devices and even lead to inaccuracies in the extraction of the device parameters. Here, we demonstrate a simple and efficient strategy for reducing the contact resistance in organic thin-film transistors by more than an order of magnitude by creating high work function domains at the surface of the injecting electrodes to promote channels of enhanced injection. We find that the method is effective for both organic small molecule and polymer semiconductors, where we achieved a contact resistance as low as 200 Ωcm and device charge carrier mobilities as high as 20 cm2V−1s−1, independent of the applied gate voltage., Minimizing contact effects in organic semiconductor-based devices is a key step toward the development of a low-cost technology for next-generation electronics. Here, the authors reduce contact resistance in organic devices by engineering electrodes with high work function surface domains.

In hybrid halide perovskite, the effectiveness of charge transport in relation to film microstructure and processing has remained elusive. In this study we succeeded in tuning grain size and grain boundary chemistry through solvent vapor annealing, which resulted in an increase in charge-carrier mobility by one order of magnitude. To understand the mechanism responsible for the enhanced charge transport, we performed a series of complementary measurements. Atomic force microscopy revealed an increase in grain size and uniformity, and optical microscopy showed a macroscopic reorganization of the film structure. X-ray diffraction measurements of the MAPbI3-xClx films confirmed the removal of preferential orientation after 20 min of solvent annealing at room temperature, in N,N-dimethylformamide. The presence of additional peaks was assigned to the formation of the solvent complex MAI:DMF:PbI2 and the PbI2:DMF ligand, and the content of these phases was monitored as a function of annealing time. Charge-carrier mobility was evaluated from field-effect transistor measurements in devices with gold top contacts and SiO2 bottom-gate dielectric. We obtained ambipolar transport, with both hole and electron mobility exceeding 10cm2/Vs at room temperature. We propose that this remarkable enhancement in electrical properties resulted from an increase in the grain size and passivation of grain boundaries via formation of intermediate solvent complexes formed from unreacted material. This work has allowed us to gain unprecedented insight into the impact of film morphology on charge transport in perovskite materials, an important milestone towards achieving high-performance optoelectronic devices such as transistors, photovoltaics, light emitting diodes, and photodetectors.

Expression of neuregulin-2 (NRG2) is intense in a few regions of the adult brain where neurogenesis persists; however, little is understood about its role in developments of newborn neurons. To study the role of NRG2 in synaptogenesis at different developmental stages, newborn granule cells in rat hippocampal slice cultures were labeled with retrovirus encoding tetracycline-inducible microRNA targeting NRG2 and treated with doxycycline (Dox) at the fourth or seventh postinfection day (dpi). The developmental increase of GABAergic postsynaptic currents (GPSCs) was suppressed by the early Dox treatment (4 dpi), but not by late treatment (7 dpi). The late Dox treatment was used to study the effect of NRG2 depletion specific to excitatory synaptogenesis. The Dox effect on EPSCs emerged 4 d after the impairment in dendritic outgrowth became evident (10 dpi). Notably, Dox treatment abolished the developmental increases of AMPA-receptor mediated EPSCs and the AMPA/NMDA ratio, indicating impaired maturation of glutamatergic synapses. In contrast to GPSCs, Dox effects on EPSCs and dendritic growth were independent of ErbB4 and rescued by concurrent overexpression of NRG2 intracellular domain. These results suggest that forward signaling of NRG2 mediates GABAergic synaptogenesis and its reverse signaling contributes to dendritic outgrowth and maturation of glutamatergic synapses.SIGNIFICANCE STATEMENTThe hippocampal dentate gyrus is one of special brain regions where neurogenesis persists throughout adulthood. Synaptogenesis is a critical step for newborn neurons to be integrated into preexisting neural network. Because neuregulin-2 (NRG2), a growth factor, is intensely expressed in these regions, we investigated whether it plays a role in synaptogenesis and dendritic growth. We found that NRG2 has dual roles in the development of newborn neurons. For GABAergic synaptogenesis, the extracellular domain of NRG2 acts as a ligand for a receptor on GABAergic neurons. In contrast, its intracellular domain was essential for dendritic outgrowth and glutamatergic synapse maturation. These results imply that NRG2 may play a critical role in network integration of newborn neurons.

Alterations in mitochondrial DNA (mtDNA) have been studied in various cancers. However, the clinical value of mtDNA copy number (mtCN) alterations in gastric cancer (GC) is poorly understood. In the present study, we investigated whether alterations in mtCNs might be associated with clinicopathological parameters in GC cases. mtCN was measured in 109 patients with GC by real-time PCR. Then, correlations with clinicopathological characteristics were analyzed. mtCN was elevated in 64.2% of GC tissues compared with paired, adjacent, non- cancerous tissue. However, the observed alterations in mtCN were not associated with any clinicopathological characteristics, including age, gender, TN stage, Lauren classification, lymph node metastasis, and depth of invasion. Moreover, Kaplan-Meier survival curves revealed that mtCN was not significantly associated with the survival of GC patients. In this study, we demonstrated that mtCN was not a significant marker for predicting clinical characteristics or prognosis in GC.

Colorectal cancer is a heterogeneous disorder than arises via multiple distinct pathways, from tubular adenomas (TAs) and sessile serrated adenomas (SSAs), which are clinically, morphologically, and molecularly different. We examined PIK3CA amplification in colorectal precancerous legions, including TAs and SSAs. DNA was isolated from paired normal and tumoral tissues in 64 TAs and 32 SSAs. PIK3CA amplification, KRAS mutation, and BRAF mutation were analyzed by real-time PCR and pyrosequencing. PIK3CA amplification was found in 25% of TAs and 9.4% of SSAs, respectively. KRAS and BRAF mutations were mutually exclusive in both TAs and SSAs. In TAs, PIK3CA amplification was associated with left side and it was mutually exclusive with KRAS mutation. These results suggest that PIK3CA amplification may be early and important event in colorectal carcinogenesis and may drive the development of left-side TAs independently with KRAS mutation.